Cerebrospinal fluid transferrin levels are reduced in patients with early multiple sclerosis

2014 ◽  
Vol 20 (12) ◽  
pp. 1569-1577 ◽  
Author(s):  
M Khalil ◽  
B Riedlbauer ◽  
C Langkammer ◽  
C Enzinger ◽  
S Ropele ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Biochemical Study ◽  
Iron Deposition ◽  
Lesion Load ◽  
Transporter Protein ◽  
In Cis ◽  
The Brain

Background: Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids. Objectives: The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters. Methods: We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS ( n=60) or early MS ( n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load. Results: CSF transferrin was significantly decreased in CIS/MS compared to controls ( p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores ( r= −0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load. Conclusion: Our biochemical study provides evidence that altered iron homeostasis within the brain occurs in the very early phases of the disease, and suggests that the transporter protein transferrin may play a role in the increased iron deposition known to occur in the brain of MS patients.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

2021 ◽  
Author(s):  
Sandesh Kini ◽  
Yellanthoor Ramesh Bhat ◽  
Lakshmikanth Halegubbi Karegowda
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Case Report ◽  
Demyelinating Disease ◽  
Oligoclonal Bands ◽  
Initial Manifestation ◽  
Demyelinating Disorder ◽  
The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

Neutralising and binding anti-interferon-β-1 b (IFN-b-1 b) antibodies during IFN-β-1 b treatment of multiple sclerosis

1997 ◽  
Vol 3 (3) ◽  
pp. 184-190 ◽  
Author(s):  
P. Kivisäkk ◽  
GV Alm ◽  
WZ Tian ◽  
D. Matusevicius ◽  
S. Fredrikson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Solid Phase ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Resonance Imaging ◽  
Interferon Β ◽  
Lesion Load ◽  
Neutralising Antibodies ◽  
The Brain ◽  
Antibody Secreting Cells

Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

scholarly journals Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis

2015 ◽  
Vol 21 (5) ◽  
pp. 550-561 ◽  
Author(s):  
M Alba Mañé Martínez ◽  
Bob Olsson ◽  
Laura Bau ◽  
Elisabet Matas ◽  
Álvaro Cobo Calvo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disability Progression ◽  
Neurofilament Light ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neuronal Markers ◽  
Independent Prognostic Marker ◽  
Csf Levels ◽  
In Cis ◽  
T Tau

Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.

scholarly journals Follistatin (FS) in human cerebrospinal fluid and regulation of FS expression in a mouse model of meningitis

2000 ◽  
pp. 809-816 ◽  
Author(s):  
U Michel ◽  
S Ebert ◽  
O Schneider ◽  
Y Shintani ◽  
S Bunkowski ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Specific Binding ◽  
In Situ Hybridisation ◽  
Viral Meningitis ◽  
Csf Analysis ◽  
Mrna And Protein Expression ◽  
Leukocyte Counts ◽  
The Brain

OBJECTIVE: Follistatin (FS) is the specific binding protein of activin and expression of both factors is regulated by inflammatory agents. Therefore, FS concentrations were determined in cerebrospinal fluid (CSF) of patients with bacterial and viral meningitis or multiple sclerosis (MS), as well as in the CSF of patients without meningial inflammation or autoimmune diseases. Furthermore, a mouse pneumococcal meningitis model was used to localise the cellular sources of FS in brains of normal and meningitic mice. METHODS: FS concentrations in CSF were determined by ELISA; FS in mice was localised by in situ hybridisation and immunohistochemistry. RESULTS: FS concentrations were > or =0.4 microg/l in 22 of 66 CSF samples of meningitis patients versus 2 of 27 CSF samples from patients with multiple sclerosis (P<0.05) and 2 of 41 CSF specimen from patients without neuroinflammatory diseases (P<0.01). In the CSF of patients with meningitis, the concentration of FS was correlated with total protein (P<0.005) and lactate concentrations (P<0.05), but not with leukocyte counts, interval between onset of disease and CSF analysis, or clinical outcome. The CSF-to-serum ratios of FS and albumin also correlated significantly (P<0.0005). In some patients with meningitis the CSF-to-serum ratios suggested that the elevated FS in CSF did not originate from serum alone. FS was localised in mice brains to neurones of the hippocampus, dentate gyrus, neocortex, and to the choroid plexus. Analyses of brains and other organs from uninfected and infected animals sacrificed 6-36 h after infection did not reveal any obvious differences in the distribution and intensity of FS mRNA and protein expression. CONCLUSIONS: The concentration of FS in humans is elevated during meningitis. In some patients the increase is caused by a release of FS from brain into CSF. Data from the mouse meningitis model suggest that increased CSF concentrations of FS in meningitis appear not to be accompanied by an elevated number of cells containing FS mRNA or protein in the brain.

Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course

2010 ◽  
Vol 17 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Mohsen Khademi ◽  
Ingrid Kockum ◽  
Magnus L Andersson ◽  
Ellen Iacobaeus ◽  
Lou Brundin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Bacterial Infections ◽  
Neurological Diseases ◽  
Activity Levels ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Diagnostic Work ◽  
In Cis ◽  
Work Up

Background: Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments. Objective: Here we validate the potential role of CSF CXCL13 as a biomarker for aspects of MS in a large amount of clinical material, the majority collected at early diagnostic work-up. Methods: CXCL13 was measured by ELISA in 837 subjects: relapsing–remitting MS (RRMS; n = 323), secondary progressive MS (SPMS; n = 40), primary progressive MS (PPMS; n = 24), clinically isolated syndrome (CIS; n = 79), other neurological diseases (ONDs; n = 181), ONDs with signs of inflammation or viral/bacterial infections (iONDs; n = 176) and healthy controls ( n = 14). Results: Subjects with viral/bacterial infections had extremely high CXCL13 levels compared to all included groups ( p < 0.0001). CXCL13 was otherwise significantly higher in MS compared to the remaining controls ( p < 0.0001), and CIS ( p < 0.01). A significant and positive correlation between CXCL13 and relapse rate, the results obtained for the Expanded Disability Status Scale (EDSS) and the number of lesions detected by MRI was demonstrated. CXCL13 was increased in CIS conversion to clinically definite MS ( p < 0.001). Oligoclonal immunoglobulin band (OCB)-positive CIS or MS had significantly increased CXCL13 levels compared to OCB-negative CIS or MS ( p < 0.001 and p < 0.0001, respectively). Conclusion: CXCL13 was associated with disease exacerbations and unfavourable prognosis in RRMS. Increased CXCL13 was not specific for MS since subjects with viral/bacterial infections exhibited even higher levels. High levels predicted CIS conversion to MS. We suggest that measurement of CSF CXCL13 can be part of the armamentarium in the diagnostic and prognostic work-up in MS and be of help in future treatment decisions.

scholarly journals Multiple Sclerosis in the Emirati Population: Onset Disease Characterization by MR Imaging

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Manzoor Ahmed ◽  
Ruqqiya Mir ◽  
Mustafa Shakra ◽  
Safana Al Fardan
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Age Of Onset ◽  
Female Dominance ◽  
Cervical Cord ◽  
Gulf Region ◽  
Lesion Load ◽  
Disseminated Disease ◽  
Brain And Spinal Cord ◽  
The Brain

Background and Objectives. Multiple Sclerosis (MS) epidemiology is on the path of globalization mainly due to changing environmental factors. The prevalence of MS is on the rise in the Middle East and Persian Gulf region. Our observations has led us to hypothesize a heavy MRI lesion load at the onset of disease in a relatively younger native population. We aimed to estimate and characterize the onset disease on MRI using McDonald’s criteria while applying its terms of “Dissemination in Space (DIS) and Dissemination in Time (DIT)”. Materials and Methods. Retrospective review of onset MRI studies of 181 Emirati (native) individuals. Basic demographics were captured. Only 47 patients with Clinically Definite MS (CDMS) were included who had onset diagnostic MRI available. Lesion load was quantified using the specific zones of involvement designated for DIS: (1) Periventricular (PVZ) (I), (2) Juxta-cortical (II) (3) Infra-tentorial (III) and, (4) Spinal cord (IV). PVZ was sub-classified and lesions were quantified. A single enhancing lesion was required for DIT. Results. Average age of onset was about 26 years with female dominance of about 2 : 1. About 50% had all 4 zones and about 85% had at least 3 zones involved at the onset. Involvement of only 1 zone was rare. Dissemination in time (DIT) in brain and/or cord was present in approximately 50%. Each of the 4 zones were involved in at least 70% of cases. PVZ was not spared in any case with at least 3 lesions present in approx. 95% and ≥12 lesions in approx. half of the patients. Spinal cord specifically cervical cord was involved in up to 80% with typical patchy lesions. Conclusion. Onset disease characterization using MRI in a young Emirati cohort showed a heavy lesion load in the brain and spinal cord at the onset, signifying cumulative disease before presentation. Disseminated disease also facilitated early diagnosis of MS. The findings have significant potential ramifications for local environmental and cultural factors, as well as disease course and disability progression.

Early Diagnosis of Multiple Sclerosis Based on Optical and Electrochemical Biosensors: Comprehensive Perspective

2020 ◽  
Vol 16 (5) ◽  
pp. 557-569 ◽  
Author(s):  
Maryam Kharati ◽  
Sanam Foroutanparsa ◽  
Mohammad Rabiee ◽  
Reza Salarian ◽  
Navid Rabiee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Early Detection ◽  
Diagnostic Methods ◽  
Electrochemical Biosensors ◽  
Non Invasive ◽  
Biosensor System ◽  
Brain And Spinal Cord ◽  
The Brain

Background: Multiple Sclerosis (MS) involves an immune-mediated response in which body’s immune system destructs the protective sheath (myelin). Part of the known MS biomarkers are discovered in cerebrospinal fluid like oligoclonal lgG (OCGB), and also in blood like myelin Oligodendrocyte Glycoprotein (MOG). The conventional MS diagnostic methods often fail to detect the disease in early stages such as Clinically Isolated Syndrome (CIS), which considered as a concerning issue since CIS highlighted as a prognostic factor of MS development in most cases. Methods: MS diagnostic techniques include Magnetic Resonance Imaging (MRI) of the brain and spinal cord, lumbar puncture (or spinal tap) that evaluate cerebrospinal fluid, evoked potential testing revealing abnormalities in the brain and spinal cord. These conventional diagnostic methods have some negative points such as extensive processing time as well as restriction in the quantity of samples that can be analyzed concurrently. Scientists have focused on developing the detection methods especially early detection which belongs to ultra-sensitive, non-invasive and needed for the Point of Care (POC) diagnosis because the situation was complicated by false positive or negative results. Results: As a result, biosensors are utilized and investigated since they could be ultra-sensitive to specific compounds, cost effective devices, body-friendly and easy to implement. In addition, it has been proved that the biosensors on physiological fluids (blood, serum, urine, saliva, milk etc.) have quick response in a non-invasive rout. In general form, a biosensor system for diagnosis and early detection process usually involves; biomarker (target molecule), bio receptor (recognition element) and compatible bio transducer. Conclusion: Studies underlined that early treatment of patients with high possibility of MS can be advantageous by postponing further abnormalities on MRI and subsequent attacks. : This Review highlights variable disease diagnosis approaches such as Surface Plasmon Resonance (SPR), electrochemical biosensors, Microarrays and microbeads based Microarrays, which are considered as promising methods for detection and early detection of MS.

Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis

2014 ◽  
Vol 21 (4) ◽  
pp. 396-401 ◽  
Author(s):  
C Tortorella ◽  
V Direnzo ◽  
P Taurisano ◽  
R Romano ◽  
M Ruggieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Attentional Control ◽  
Repeated Measures ◽  
Imaging Data ◽  
Neurofilament Light Chain ◽  
Recruitment Pattern ◽  
Neurofilament Light ◽  
Random Effects Models ◽  
In Cis

Background: Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. Objective: The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. Methods: Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data ( p<0.05 corrected). Results: Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with “low NFL levels” showed greater activity in the putamen compared with subjects with “high NFL levels” ( p=0.001). These results are independent of cognitive impairment index. Conclusions: Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS.

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